Figure 4.

Metabolome reveals Warburg-like metabolic switch in AD iNs

(A) Colorimetric assay to determine PKM activity in control (n = 7) and AD (n = 6) iNs (Mann-Whitney test).

(B) Colorimetric assay to detect secreted lactate in the supernatant of control (n = 9) and AD (n = 10) iNs.

(C) Density plot of PC7 of 160 metabolites measured by UHPLC-MS of control (n = 10) and AD (n = 10) iNs.

(D) Integrative transcriptomics and metabolomics (IMPaLa) analysis showing over-represented pathways including gene and metabolites rich factors.

(E) UHPLC-MS metabolic landscape in control (left; n = 10) and AD (right; n = 10) iNs. Circles represent Z scores of respective metabolites. Size and color of the font indicate the RNA-seq expression levels of related enzymes.

(F) Glucose consumption measured as the drop of extracellular glucose after 6 h in culture.

(G) Combined averages of all detected glycolytic metabolites in iNs.

(H and I) Tracing of isotope-labeled glucose after 6-h incubation with ¹³C₆-glucose. Fraction of labeled glucose detected in lactate and citrate (n = 10 per group).

Dots represent individual donors throughout the figure. Bars, mean; error bars, SD; violin plots, median and quartiles. Significance: unpaired t test, ^∗p < 0.05, ∗∗p<0.01.